An Ex Vivo and In Silico Study Providing Insights into the Interplay of Circulating miRNAs Level, Platelet Reactivity and Thrombin Generation: Looking beyond Traditional Pharmacogenetics
| Autor: | Pierre Fontana, Séverine Nolli, Sylvie Dunoyer-Geindre, Alix Garcia, Jean-Luc Reny |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Thrombin generation In silico cardiovascular disorders Medicine (miscellaneous) 030204 cardiovascular system & hematology Bioinformatics Article 03 medical and health sciences 0302 clinical medicine In vivo microRNA Medicine Platelet Platelet aggregation miRNA ddc:616 business.industry Biomarker Cardiovascular disorders Circulating MicroRNA 030104 developmental biology platelet aggregation thrombin generation Biomarker (medicine) biomarker business MiRNA Ex vivo Pharmacogenetics |
| Zdroj: | Journal of Personalized Medicine, Vol. 11, No 5 (2021) P. 323 Journal of Personalized Medicine Volume 11 Issue 5 Journal of Personalized Medicine, Vol 11, Iss 323, p 323 (2021) |
| ISSN: | 2075-4426 |
| Popis: | Platelet reactivity (PR), a key pharmacodynamic (PD) component of the action of antiplatelet drugs in cardiovascular disease (CVD) patients, is highly variable. PR is associated with occurrence or recurrence of thrombotic and bleeding events, but this association is modulated by several factors. Conventional pharmacogenetics explains a minor part of this PR variability, and among determinants of PR, circulating microRNAs (miRNAs) have been the focus of attention during these last years as biomarkers to predict PR and clinical outcomes in CVD. This being said, the impact of miRNAs on platelet function and the mechanisms behind it are largely unknown. The level of a set of candidate miRNAs including miR-126-3p, miR-150-5p, miR-204-5p and miR-223-3p was quantified in plasma samples of stable CVD patients and correlated with PR as assessed by light-transmission aggregometry and in vivo thrombin generation markers. Finally, miRNA target networks were built based on genes involved in platelet function. We show that all candidate miRNAs were associated with platelet aggregation, while only miR-126-3p and miR-223-3p were positively correlated with in vivo thrombin generation markers. In silico analysis identified putative miRNA targets involved in platelet function regulation. Circulating miRNAs were associated with different aspects of platelet reactivity, including platelet aggregation and platelet-supported thrombin generation. This paves the way to a personalized antithrombotic treatment according to miRNA profile in CVD patients. |
| Databáze: | OpenAIRE |
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